Journal of Clinical Oncology, Vol 17, Issue 3
(March), 1999: 832
© 1999 American Society for Clinical Oncology
Metastasis Stage, Adjuvant Treatment, and Residual Tumor Are Prognostic Factors for Medulloblastoma in Children: Conclusions From the Children's Cancer Group 921 Randomized Phase III Study
Paul M. Zeltzer,
James M. Boyett,
Jonathan L. Finlay,
A. Lel Albright,
Lucy B. Rorke,
Jerrold M. Milstein,
Jeffrey C. Allen,
Kenneth R. Stevens,
Philip Stanley,
Hao Li,
Jeffrey H. Wisoff,
J. Russell Geyer,
Patsy McGuire-Cullen,
James A. Stehbens,
Susan B. Shurin,
Roger J. Packer
From the University of California at Irvine Medical Center, Orange, Neurosurgical Institute, Cedars Sinai Medical Center, Los Angeles, and Childrens Hospital, Los Angeles, CA; St. Jude Children's Research Hospital, Memphis, TN; Memorial Sloan-Kettering Cancer Center, Beth Israel Medical Center, and New York University Medical Center, New York, NY; Children's Hospital of Pittsburgh, Pittsburgh, and Children's Hospital of Philadelphia, Philadelphia, PA; Children's Hospital and Medical Center, Seattle, WA; Doernbecher Children's Hospital, Portland, OR; Childrens Hospital of Denver, Denver, CO; Department of Pediatrics, University of Iowa, Iowa City, IA; Cleveland Rainbow Babies Hospital, Cleveland, OH; and Children's National Medical Center, Washington, DC.
Address reprint requests to Paul M. Zeltzer, MD, Children's Cancer Group, PO Box 60012, Arcadia, CA 91066-6012.
PURPOSE: From 1986 to 1992, "eight-drugs-in-one-day" (8-in-1) chemotherapy both before and after radiation therapy (XRT) (54 Gy tumor/36 Gy neuraxis) was compared with vincristine, lomustine (CCNU), and prednisone (VCP) after XRT in children with untreated, high-stage medulloblastoma (MB).
PATIENTS AND METHODS: Two hundred three eligible patients with an institutional diagnosis of MB were stratified by local invasion and metastatic stage (Chang T/M) and randomized to therapy. Median time at risk from study entry was 7.0 years.
RESULTS: Survival and progression-free survival (PFS) ± SE at 7 years were 55% ± 5% and 54% ± 5%, respectively. VCP was superior to 8-in-1 chemotherapy, with 5-year PFS rates of 63% ± 5% versus 45% ± 5%, respectively (P = .006). Upon central neuropathology review, 188 patients were confirmed as having MB and were the subjects for analyses of prognostic factors. Children aged 1.5 to younger than 3 years had inferior 5-year estimates of PFS, compared with children 3 years old or older (P = .0014; 32% ± 10% v 58% ± 4%, respectively). For MB patients 3 years of age or older, the prognostic effect of tumor spread (M0 v M1 v M2+) on PFS was powerful (P = .0006); 5-year PFS rates were 70% ± 5%, 57% ± 10%, and 40% ± 8%, respectively. PFS distributions at 5 years for patients with M0 tumors with less than 1.5 cm2 of residual tumor, versus  1.5 cm2 of residual tumor by scan, were significantly different (P = .023; 78% ± 6% v 54% ± 11%, respectively).
CONCLUSION: VCP plus XRT is a superior adjuvant combination compared with 8-in-1 chemotherapy plus XRT. For patients with M0 tumors, residual tumor bulk (not extent of resection) is a predictor for PFS. Patients with M0 tumors, 3 years with  1.5 cm2 residual tumor, had a 78% ± 6% 5-year PFS rate. Children younger than 3 years old who received a reduced XRT dosage had the lowest survival rate.
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